Inclusion Criteria:
* Histologically (or cytologically) confirmed metastatic melanoma.
* Unresectable Stage III or Stage IV metastatic melanoma.
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* Subjects with no history of brain metastases demonstrated by a baseline MRI, or subjects with a history of previously treated brain metastases who have history of operable/SRS treatable brain metastases and completed surgical resection/stereotactic radiosurgery with or without adjuvant whole brain radiation at least 28 days prior to Day 1; have baseline MRI that shows no evidence of active intercranial disease; have discontinued taking medications for symptom management of brain metastases at least 7 days prior to Day 1
* 28 days since prior anti-cancer therapy.
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
* Adequate hematologic, renal and hepatic function.
* Partial Thromboplastin Time (PTT) is \<= 1.5 x upper normal limit of institution's normal range and international normalized ratio (INR) \< 1.5.
* Subject's with significant fluid retention may be allowed at the discretion of the investigator.
* Life expectancy \> 12 weeks.
* Females must not be pregnant.
* Voluntarily signed informed consent.
Exclusion Criteria:
* Lactate Dehydrogenase (LDH) \> 2 x Upper Limit of Normal (ULN).
* Ocular malignant melanoma.
* History of central nervous system metastases or leptomeningeal disease.
* Prior treatment with Dacarbazine (DTIC) or Temozolomide (TMZ).
* Prior DNA damaging agents or cytotoxic chemotherapy.
* Prior Whole Brain Radiation Therapy (with exceptions).
* Received an investigational agent within 28 days of study.
* History of seizure disorder and/or taking medication for seizure disorder.
* Active malignancy within the past 5 years, except cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.
* Medical condition that would cause a high risk for toxicities.
