Santana, a converted infielder who is rated the Tribe's No. 1 prospect and 11th overall on MLB.com's Top 50 Prospects, went 4-for-16 in eight Cactus League games and impressed manager Manny Acta with his game-calling improvement.
"But he's not a finished product. He needs to work on every part of his game, and we have to compete with the guys we have here," Acta said prior to Friday's game here against the Giants. "But he's so talented. He's gifted.
"Calling the game is not a big issue for him; he did great here. It's pretty clear what we expect. There's no timetable for [his promotion]. It's up to him."
Brown, who copped a batting title last year in the Triple-A International League, tore the meniscus in his right knee during drills two weeks ago. He and Santana were among the four optioned to Columbus, along with right-handers Jeanmar Gomez and Hector Rondon.
Additionally, infielder Brian Bixler, who was out of options and thus first had to clear waivers, was outrighted to Columbus.
Infielder Carlos Rivero and outfielder Nick Weglarz were optioned to Double-A Akron.
Also, infielder Beau Mills was reassigned to the Minor League camp.
The 47 players remaining in camp include 22 pitchers, 13 infielders, seven outfielders and five catchers.
Tom Singer is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.