 - Known CNS metastasis, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging MRI or CT during the screening period. Anticonvulsants stable dose are allowed. Treatment for brain metastases may include whole brain radiotherapy WBRT, radiosurgery RS; Gamma Knife, LINAC, or equivalent or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded. 