 14. Treatment to central nervous system lesions, such as the brain or spine prior to first line systemic therapy, or symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization, in which case the patient would be randomized to treatment of other metastatic sites or the primary sites based on the disease remaining after first-line treatment. These treated lesions should be counted towards the total number of metastases at the time of enrollment. 