Inclusion Criteria:

• Cohort A:
• No prior local therapy for brain metastases.
• Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 3 weeks prior to first dose of study treatment.
• No prophylactic or preventive anti-epileptic therapy. Exception: anti-epileptic therapy indicated in order to prevent neurologic symptoms caused by a pre-existing condition and not related to brain metastasis is allowed.
• Cohort B:
• Subjects must have received at least one local therapy for brain metastases including but not restricted to brain surgery, Whole Brain Radiotherapy or Stereotactic Radiosurgery (e.g. gamma knife, linear-accelerated-based radiosurgery, charged particles, and CyberKnife). Multiple local therapies or combinations of local therapies are allowed. For subjects receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For subjects receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated.
• Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to first dose of study treatment.
• Prophylactic or preventive anti-epileptic therapy is allowed.
• General:
• Must sign written informed consent.
• Must be at least 18 years of age.
• Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600E- or V600K-mutation.
• Up to two previous treatment regimens for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy.
• At least one measurable intracranial target lesion for which all of the following criteria have to be met:
• previously untreated or progressive according to RECIST 1.1 (greater than or equal to 20% increase in longest diameter on baseline scan) after previous local therapy
• immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy
• largest diameter of greater than or equal to 0.5cm but less than or equal to 4 cm as determined by contrast-enhanced MRI
• for target lesions (for definition see Section 6.1.1) with diameter of greater than 0.5 cm but less than or equal to 1 cm documented measurement by a neuroradiologist is required.
• for all lesions with diameter of greater than or equal to 3 cm but less than or equal to 4 cm documented measurement by a neuroradiologist is required.
• Time interval between last day of previous anti-tumour systemic treatment and first dose of GSK2118436:
• 14 days elapsed from last treatment with surgery, SRS or gamma knife
• 28 days elapsed from last treatment with WBRT
• Greater than or equal to 28 days or five half-lives (whichever is longer) have elapsed from last dose of approved or investigational chemo-, cytokine-, immune-, biological-, or vaccine-therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Adequate organ function.
• Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment.

Exclusion Criteria:

• Neurological symptoms related to brain metastasis.
• Previous treatment with a BRAF or MEK inhibitor.
• Current or expected use of a prohibited medication during treatment with GSK2118436.
• Presence of leptomeningeal disease or primary dural metastases.
• Known allergies against contrast agents required for magnetic resonance imaging (MRI) of intracranial lesions.
• Current use of therapeutic warfarin. NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted.
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia.
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
• A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
• Acute infection requiring intravenous antibiotics
• History of another malignancy. Exception: (a) Subjects who have been disease-free for 5 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from melanoma target and non-target lesions are eligible.
• Certain cardiac abnormalities.